June 15, 2009 - The Centers for Disease Control and Prevention (CDC)
today released recommendations for best practices in genetic testing for
heritable diseases and conditions. Published online June 12 in the
Morbidity and Mortality Weekly Report, the recommendations are the first
issued by the federal government regarding the accuracy and proper use
of DNA-based genetic testing.

The CDC, together with the Centers for Medicare & Medicaid Services
(CMS), has worked with the Clinical Laboratory Improvement Advisory
Committee (CLIAC) to review quality concerns related to molecular
genetic testing. The newly released report reflects CLIAC
recommendations of "good laboratory practices for ensuring the quality
of molecular genetic testing for heritable diseases and conditions."

A significant concern in molecular genetic testing is erroneous results.
This report cites previous studies that show more errors originating
during preanalytic and postanalytic phases of testing than during the
analytic process itself. Inappropriate test selection underlies many
preanalytic errors - a study of testing for the adenomatous polyposis
coli gene found that testing was unwarranted in 17% of the cases.

During the analytic phase, errors in specimen handling and analysis have
been reported in 0.06% to 0.12% of nearly 100,000 tests studied.
Postanalytic errors commonly reflect problems in preparing reports and
interpreting results. Studies have shown that a major contributor to
these problems is poor understanding among healthcare providers of the
limitations of molecular genetic tests and their proper interpretation.

The present recommendations drew on information from government reports,
scientific publications, the CMS CLIA database, studies carried out by
professional groups, state programs, and a variety of laboratory
directories and databases. Members of the CLIAC Genetic Testing Good
Laboratory Practices Workgroup evaluated factors in genetic testing
likely to affect quality and identified areas in need of quality
assurance guidelines to comply with current CLIA requirements. The
practices recommended relate specifically to testing for heritable
diseases.

Preanalytic Testing Phase Guidelines
In the preanalytic testing phase, the report lists the following
guidelines for laboratories in providing information about molecular
genetic tests to those who use their services:

* Selection of appropriate tests;
* Information on proper methods for collecting, handling,
transporting, and submitting specimens;
* Patient information needed for proper testing and
reporting of results;
* Indication of potential implications of the results for
family members; and
* Availability of laboratory consultations regarding the
issues mentioned earlier.

Additional concerns addressed by the workgroup in the preanalytic phase
were informed consent, test requests, specimen handling, and
establishing policies to assess and correct problems.

Analytic Testing Phase Guidelines
The analytic phase of molecular genetic testing has already been
regulated by CLIA requirements to "establish or verify the analytic
performance of all nonwaived tests and test systems before introducing
them for patient testing." Beyond adherence to the more general CLIA
requirements, recommendations for molecular and genetic testing focus on
the assurance of validity and reliability in the tests and in the proper
interpretation of test results.

The recommendations list 5 guidelines regarding establishing and
verifying performance specifications for each genetic test:

* "Conduct a review of available scientific studies and
pertinent references
* Define appropriate patient populations for which the
test should be performed
* Select the appropriate test methodology for the disease
or condition being evaluated
* Establish analytic performance specifications and
determine quality control procedures using the appropriate number, type,
and variety of samples
* Ensure that test results and their implications can be
interpreted for an individual patient or family and that the limitations
of the test are defined and reported."

The recommendations for the analytic phase devote significant attention
to control procedures and emphasize the importance of proficiency
testing in evaluating laboratory competence (as well as in providing
education for lab personnel).

Postanalytic Testing Phase Guidelines
Recommendations for the postanalytic testing phase focus on the content,
completeness, and interpretation of test reports. In addition, CLIA
requires that test reports, records, and even the tested specimens be
retained for specified periods, ranging from "as long as possible" for
tested specimens to 2 years for test reports and 10 years for pathology
test reports. These recommendations recognize the potential importance
of these materials for family members and for future diagnostic use as
medical technology and knowledge progress.

Finally, the report speaks to issues of confidentiality, laboratory
personnel, and the "quality management system" approach - a system
widely adopted internationally but less common in the United States.
Development of a quality management system is likely to play an
important role in the ability of labs to receive test referrals from
international sources, as well as in improving their quality management.

Although CLIAC recommendations have now been made, the authors emphasize
that they are in no sense complete: "Continual monitoring of the
practice and test performance of molecular genetic tests is needed to
evaluate the effectiveness of these recommendations and to develop
additional guidelines for good laboratory practices," they conclude.

Morb Mortal Wkly Rep. 2009;58(RR-6):1-37.